HPV-associated cervical cancers show frequent allelic loss at 3p14 but no apparent aberration of FHIT mRNA.
The genetic aberration involved in the loss of heterozygosity (LOH) at 3p14 has recently been attributed to the disruption of the FHIT gene in many cancers. This study analyzed HPV DNA and allelic status of 5 microsatellite markers spaning 3p13-3p25 in 57 cases of cervical cancer. With no homozygous deletion found in any case, a 39% overall frequency of LOH was noted. The presence of tumorigenic HPV DNA (91%) did not correlate with the allelic loss at any marker, including THRB (3p22-24) and D3S1228 (3p14) which were found with high LOH rates of 43% (12/28) and 37% (11/30), respectively. Further analysis of FHIT mRNA in 29 cancers by reverse transcription (RT)-PCR showed a full-length transcript in all cases. However, additional minor transcripts were occasionally observed in cancer tissues (9/29) as well as in normal tissues (12/31) by nested PCR of the RT products. Sequence analysis of these transcripts showed exclusive internal exon deletions, suggesting a source of minor splicing variants. No apparent mutation of the mRNA sequences was found in 8 transcripts examined, except for a silent polymorphism and a site of alternative splicing. The results suggest that, although frequently reported to be abrogated in several cancers, the mRNA of FHIT remains intact in cervical cancer. Other genes closely linked to FHIT may be responsible for frequent LOH at 3p14 observed in cervical cancer.
Chu
T Y
TY
Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China. tychu@email.gcn.net.tw
Shen
C Y
CY
Chiou
Y S
YS
Lu
J J
JJ
Perng
C L
CL
Yu
M S
MS
Liu
H S
HS
D017766:Acid Anhydride Hydrolases; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002893:Chromosomes, Human, Pair 3; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics*; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D011506:Proteins; D012333:RNA, Messenger; D000099170:Bis(5'-adenosyl)triphosphatase